Matt McCarthy

This is one of the first rivalry weekends of the college football season, and I'll be spending it in New Haven, Connecticut, for what is perhaps the nadir of intercollegiate gridiron competition: the Harvard/Yale game. Inside the stadium, the future business leaders of America will strap on the pads and play what is expected to be a high-scoring, somewhat sloppy affair; but outside of the stadium, my friends and I will look on as thousands of twenty-somethings consume preposterous amounts of alcohol in an open field. The next day, many of these co-eds (and many more of us old farts) will wake up feeling shaky, with pounding headaches, nausea, fatigue, and perhaps a splash of diarrhea. Many will swear they're never drinking again. I know I've made that promise at least a dozen times.

The hungover body is clearly trying to tell us something, but what exactly is it saying?

OK, so what causes a hangover?

There is no consensus definition of what constitutes a hangover but we all have a general understanding of what one is. The symptoms usually occur eight to sixteen hours after we booze and are caused by a toxic blend of dehydration, hormonal alterations, release of inflammatory molecules, electrolyte imbalances and blood sugar swings. When you're drunk, the heart works harder but the brain slows down1 and has trouble secreting something called antidiuretic hormone (ADH) which is a molecule that helps the body retain water.When ADH production shuts down, water pours out of the kidney, leading many of us "break the seal" and urinate with embarrassing frequency.

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This liquid exodus causes dehydration and for some, the urge to consume even more alcohol. This is a mistake. The next cocktail further inhibits the production of ADH, which causes worsening dehydration and that, in turn, can lead to troubling electrolyte imbalances. But dehydration is not the only explanation for the hangover. While you're drinking, the body metabolizes alcohol into a noxious chemical called acetaldehyde by a liver enzyme called alcohol dehydrogenase. At high concentrations, acetaldehyde is able to produce the nasty symptoms of ﬂush syndrome: tachycardia, cold sweats, nausea, and vomiting.Many researchers believe that dehydration isn't really the problem; rather, it's the toxic levels of acetaldehyde as well as other preservatives that cause the hangover.2

But there's more to the story. While you're doing those keg stands, the rapid infusion of alcohol causes blood vessels to dilate, including those that feed the brain, and that is what's primarily responsible for the pounding headache. The body also experiences alterations in blood levels of serotonin and histamine, which likely account for the flushing and diarrhea. But scientists like to disagree, and some suggest that these biochemical fluctuations are irrelevant and that the hangover is really just the first sign of alcohol withdrawal. They point out that the symptoms are most pronounced when the blood alcohol level researches zero and that the painful symptoms subside with further alcohol consumption, something known as "hair of the dog."

Are there any super weird theories?

Funny you should ask! Newer research suggests that those tequila shots make us feel like crap for a radically different reason. In one study—a study where people were actually paid to get drunk—twenty healthy men with a history of hangovers were asked to abstain from food, coffee, and physical exercise starting at 4:00 p.m. and were given a mixture of 23% alcohol and orange juice at 7:00 p.m. The subjects drank the cocktail within 60 min (10-min intervals) and were told to read books or to have conversations—perhaps about college football—but they were forbidden from exercise (no dancing or running). They were instructed to sleep from 11:00 p.m. until to 7:00 a.m. and blood samples were obtained that morning, just as the hangovers were setting in.

The results were surprising and suggest that as we overindulge in alcohol, the immune system is activated and a number of inflammatory markers, including interleukin-10, interleukin-12, and interferon-gamma are released into the bloodstream. Interleukin-10 has been shown to cause a flu-like syndrome when it's injected into healthy volunteers; the other two molecules have been shown to set off an inflammatory cascade which may cause the other symptoms—nausea, tremors, diarrhea—that frequently accompany the hangover. The bad news is that the body treats alcohol like it's an infection; the good news is that we may be able to decrease the level of these inflammatory molecules with simple over-the-counter medications like Ibuprofen.3

So what's the most scientific cure for a hangover?

Well, it kind of depends. We'd do well to remember that excess alcohol consumption is called intoxication because booze really is a toxic substance and that having a hangover isn't all that different than having the flu. So just as the symptoms may vary, it seems that the cure for a hangover does, too.

It often takes more than a couple of Ibuprofen and a Gatorade for me to feel better. Caffeine, oxygen, sugar, and vitamin B6 have all been used successfully as a cure for the hangover. (Some research suggests the best answer is simply coffee and aspirin.) Ernest Hemingway swore by tomato juice and beer; Ancient Romans ate raw owls eggs.There's a lot of weird stuff going on out there, actually.

One tip to live by, though, is that the less thoroughly distilled booze (typically cheaper) will give you a worse headache, as will red wine, for reasons unknown to medicine.

You. You're out drinking with your friends, matching them round for round. They're…
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So, hydrate. You should be drinking water throughout the night, since you're losing fluids as you consume alcohol. This will keep your brain from dehydrating and contracting, which strains the brain tissue and causes your 8AM migraine.

Can you drink without getting a hangover?

The Holy Grail, it would seem, is alcohol without the hangover. Might we one day have the delightful effects of alcohol without the side effects? It appears that this fantasy is now a distinct possibility. Earlier this month, a neuropharmacology professor at the Imperial College London named David Nutt claimed he had identified molecules that reproduce the pleasurable effects of alcohol but are much less toxic and would circumvent the nasty symptoms of a hangover.

In an interview with the BBC, Dr. Nutt said, "There's no question that you can produce a whole range of effects like alcohol by manipulating this system in the brain. In some experiments, the effect is indistinguishable from alcohol. What we want to do is get rid of any the unwanted effects of inebriation, like aggression and memory impairment, and we just want to keep the pleasure and the sense of relaxation. We think by clever molecular modeling we can get rid of the risk of addiction as well."

The professor likes to compare his discovery to the e-cigarette and suggests the elimination of the toxic side effects of alcohol is both a moneymaking opportunity and a public health benefit. He dreams of making a wide range of cocktails with his synthetic alcohol substitute and he's looking for investors. I bet I can find a few at the Harvard/Yale game.

2 These preservatives are known as congeners and are found primarily in brandy, wine, tequila, whiskey, and other dark liquors and increase the frequency and severity of hangover. Clear liquors, such as rum, vodka, and gin, tend to cause hangover less frequently, which may explain why patients with chronic alcoholism use these liquors disproportionately.